Monumental progress in the areas of molecular biology, virology, gene transfer technology, and human genome mapping are providing the foundation for a new area of biomedical research - somatic gene therapy. This new approach to therapy holds tremendous promise for treating, curing and potentially preventing a large spectrum of acquired and inherited diseases. The University of Pennsylvania has an excellent track record in the development of experimental models of gene therapy, in part through integrated programs in animal models at the School of Veterinary Medicine. The recruitment of Dr. James M. Wilson as the Director of a newly formed institute for Human Gene Therapy (IHGT), along with the commitment of 25 new faculty positions and 40,000 sq ft of laboratory space to this institute, is further indication of the commitment of the University of Pennsylvania to the field of gene therapy. The IGHT provides an excellent infrastructure on which to build multidisciplinary programs in gene therapy. This P30 proposal requests support for research in "Gene Therapy of Cystic Fibrosis and Genetic Diseases." The foundation of the grant is a series of core laboratories which currently exist in the IHGT. These provide technical support for the basic and clinical development of gene therapies. They include a Vector Core, Cell Morphology Core, Animal Models Core, Human Applications Laboratory, and Ion Transport Core. Approximately 50 faculty with funded research in areas relevant to the grant have been recruited to participate. These individuals form the basis for major research programs in Cystic Fibrosis, Vectors, and Genetic Diseases. A general solicitation for Development and Feasibility proposals was sent to the Faculty at the University of Pennsylvania, Wistar institute, Children's Hospital of Philadelphia, Children's Seashore House, Medical College of Pennsylvania, Hannamahn Hospital, and St. Christopher's Hospital. We received 42 proposals and selected 12 outstanding applications for inclusion in the grant.